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. 1975 Jul;56(1):79–87. doi: 10.1172/JCI108082

Preparation of 125-I-labeled human thyroxine-binding alpha globulin and its turnover in normal and hypothyroid subjects.

R R Cavalieri, F A McMahon, J N Castle
PMCID: PMC436558  PMID: 49363

Abstract

A protein with the electrophoretic, immunologic, and hormone-binding properties of thyroxine-binding globulin (TBG) has been prepared from human plasma and labeled with radioiodine (125-I) by an enzymatic method of iodination. The [125-I]TBG retained the electrophoretic and immunologic characteristics of unlabeled TBG but exhibited a partial loss of thyroxine-binding activity, as assessed by affinity chromatography. The in vivo behavior of [125I]TBG was studied in six euthyroid subjects (controls) with normal serum levels of TBG as measured both by radioimmunoassay and by determination of maximal T4-binding capacity and in four male patients with untreated primary hyperthyroidism, three of whom had elevated serum TBG. The half-time of the final slope of the plasma disappearance curve averaged 5.0 days plus or minus 1.2 (SD) in the controls and ranged from 3.9 to 109 days in the hypothyroid patients. The distribution volume was similar in the two groups, 6.7 plus or minus 1.3 vs. 7.1 plus or minus 2.1 liters. The catabolic clearance rate averaged 0.99 plus or minus 0.33 liters plasma/24 h in the controls and 0.92 plus or minus 0.46 in the hypothyroids. The absolute turnover rate of TBG, calculated from the catabolic clearance rate multiplied by the serum concentration of radioimmunoassayable TBG, averaged 17.8 plus or minus 2.1 mg/day in the controls and ranged from 14.8 to 33.2 mg/day in the hypothyroids. Among the entire group of subjects there was no correlation between the serum TBG concentration and the absolute turnover rate of TBG.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BAUMAN A., ROTHSCHILD M. A., YALOW R. S., BERSON S. A. Distribution and metabolism of I131 labeled human serum albumin in congestive heart failure with and without proteinuria. J Clin Invest. 1955 Sep;34(9):1359–1368. doi: 10.1172/JCI103184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braverman L. E., Vagenakis A. G., Foster A. E., Ingbar S. H. Evaluation of a simplified technique for the specific measurement of serum thyroxine concentration. J Clin Endocrinol Metab. 1971 Apr;32(4):497–502. doi: 10.1210/jcem-32-4-497. [DOI] [PubMed] [Google Scholar]
  3. CAVALIERI R. R. Hyperthyroidism and decreased thyroxine binding by serum proteins. J Clin Endocrinol Metab. 1961 Nov;21:1455–1468. doi: 10.1210/jcem-21-11-1455. [DOI] [PubMed] [Google Scholar]
  4. Cavalieri R. R., Castle J. N., Searle G. L. A simplified method for estimating free-thyroxine fraction in serum. J Nucl Med. 1969 Sep;10(9):565–570. [PubMed] [Google Scholar]
  5. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  6. Giorgio N. A., Jr, Tabachnick M. Thyroxine-protein interactions. V. Isolation and characterization of a thyroxine-binding globulin from human plasma. J Biol Chem. 1968 May 10;243(9):2247–2259. [PubMed] [Google Scholar]
  7. INGBAR S. H., DOWLING J. T., FREINKEL N. The purification of thyroxine-binding protein by ion-exchange resins. Endocrinology. 1957 Sep;61(3):321–326. doi: 10.1210/endo-61-3-321. [DOI] [PubMed] [Google Scholar]
  8. Inada M., Sterling K. Thyroxine transport in thyrotoxicosis and hypothyroidism. J Clin Invest. 1967 Sep;46(9):1442–1450. doi: 10.1172/JCI105636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. LEWALLEN C. G., RALL J. E., BERMAN M. Studies of iodoalbumin metabolism. II. The effects of thyroid hormone. J Clin Invest. 1959 Jan 1;38(1 Pt 1):88–101. doi: 10.1172/JCI103798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Levy R. P., Marshall J. S., Velayo N. L. Radioimmunoassay of human thyroxine-binding globulin (TBG). J Clin Endocrinol Metab. 1971 Mar;32(3):372–381. doi: 10.1210/jcem-32-3-372. [DOI] [PubMed] [Google Scholar]
  12. Marshall J. S., Pensky J., Green A. M. Studies on human thyroxine-binding globulin. VI. The nature of slow thyroxine-binding globulin. J Clin Invest. 1972 Dec;51(12):3173–3181. doi: 10.1172/JCI107144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marshall J. S., Pensky J. Studies on human thyroxine-binding globulin (TBG). I. Purification of TBG and immunologic studies on the relationship between TBG from normal persons and those with TBG "deficiency". J Clin Invest. 1969 Mar;48(3):508–515. doi: 10.1172/JCI106008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marshall J. S., Pensky J. Studies on thyroxine-binding globulin (TBG). 3. Some physical characteristics of TBG and its interaction with thyroxine. Arch Biochem Biophys. 1971 Sep;146(1):76–83. doi: 10.1016/s0003-9861(71)80043-7. [DOI] [PubMed] [Google Scholar]
  15. Morell A. G., Gregoriadis G., Scheinberg I. H., Hickman J., Ashwell G. The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem. 1971 Mar 10;246(5):1461–1467. [PubMed] [Google Scholar]
  16. OPPEHNEIMER J. H., SURKS M. I., BERNSTEIN G., SMITY J. C. METABOLISM OF IODINE-131--LABELED THYROXINE-BINDING PREALBUMIN IN MAN. Science. 1965 Aug 13;149(3685):748–750. doi: 10.1126/science.149.3685.748. [DOI] [PubMed] [Google Scholar]
  17. OPPENHEIMER J. H., SQUEF R., SURKS M. I., HAUER H. BINDING OF THYROXINE BY SERUM PROTEINS EVALUATED BY EQUILIBRUM DIALYSIS AND ELECTROPHORETIC TECHNIQUES. ALTERATIONS IN NONTHYROIDAL ILLNESS. J Clin Invest. 1963 Nov;42:1769–1782. doi: 10.1172/JCI104862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pensky J., Marshall J. S. Studies on thyroxine-binding globulin (TBG). II. Separation from human serum by affinity chromatography. Arch Biochem Biophys. 1969 Dec;135(1):304–310. doi: 10.1016/0003-9861(69)90544-x. [DOI] [PubMed] [Google Scholar]
  19. RAYMOND S. A convenient apparatus for vertical gel electrophoresis. Clin Chem. 1962 Sep-Oct;8:455–470. [PubMed] [Google Scholar]
  20. ROBBINS J., RALL J. E. Proteins associated with the thyroid hormones. Physiol Rev. 1960 Jul;40:415–489. doi: 10.1152/physrev.1960.40.3.415. [DOI] [PubMed] [Google Scholar]
  21. ROBBINS J. Reverse-flow zone electrophoresis; a method for determining the thyroxine-binding capacity of serum protein. Arch Biochem Biophys. 1956 Aug;63(2):461–469. doi: 10.1016/0003-9861(56)90062-5. [DOI] [PubMed] [Google Scholar]
  22. Refetoff S., Robin N. I., Alper C. A. Study of four new kindreds with inherited thyroxine-binding globulin abnormalities. Possible mutations of a single gene locus. J Clin Invest. 1972 Apr;51(4):848–867. doi: 10.1172/JCI106880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SANDBERG A. A., WOODRUFF M., ROSENTHAL H., NIENHOUSE S., SLAUNWHITE W. R., Jr TRANSCORTIN: A CORTICOSTEROID-BINDING PROTEIN OF PLASMA. VII. HALF-LIFE IN NORMAL AND ESTROGEN-TREATED SUBJECTS. J Clin Invest. 1964 Mar;43:461–466. doi: 10.1172/JCI104931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  25. SLAUNWHITE W. R., Jr, SANDBERG A. A. Transcortin: a corticosteroid-binding protein of plasma. J Clin Invest. 1959 Feb;38(2):384–391. doi: 10.1172/JCI103812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Socolow E. L., Woeber K. A., Purdy R. H., Holloway M. T., Ingbar S. H. Preparation of I-131-labeled human serum prealbumin and its metabolism in normal and sick patients. J Clin Invest. 1965 Oct;44(10):1600–1609. doi: 10.1172/JCI105266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sterling K., Hamada S., Takemura Y., Brenner M. A., Newman E. S., Inada M. Preparation and properties of thyroxine-binding alpha globulin (TBG). J Clin Invest. 1971 Aug;50(8):1758–1771. doi: 10.1172/JCI106665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TANAKA S., STARR P. Clinical observations on serum globulin thyroxine-binding capacity, using a simplified technique. J Clin Endocrinol Metab. 1959 Jan;19(1):84–91. doi: 10.1210/jcem-19-1-84. [DOI] [PubMed] [Google Scholar]
  29. TATA J. R. The purification of thyroxine-binding globulin and thyroxine-binding prealbumin. Clin Chim Acta. 1961 Nov;6:819–832. doi: 10.1016/0009-8981(61)90171-1. [DOI] [PubMed] [Google Scholar]
  30. Takemura Y., Hocman G., Sterling K. Thermal stability of serum thyroxine-binding proteins. J Clin Endocrinol Metab. 1971 Feb;32(2):222–224. doi: 10.1210/jcem-32-2-222. [DOI] [PubMed] [Google Scholar]
  31. Woeber K. A., Ingbar S. H. The contribution of thyroxine-binding prealbumin to the binding of thyroxine in human serum, as assessed by immunoadsorption. J Clin Invest. 1968 Jul;47(7):1710–1721. doi: 10.1172/JCI105861. [DOI] [PMC free article] [PubMed] [Google Scholar]

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